TITLE

Engineering Synthetic RNA Controllers for Biosensing Gene Regulation and Targeted Therapies

ABSTRACT

     Synthetic RNA circuits are engineered to precisely control cellular information flow, with applications in biosensing, gene therapy, and biomanufacturing. To design and implement RNA-based input/output systems, we utilized aptamers for sensing, ribozymes, RNA switches, and translation enhancers for gene regulation, and computational models for design optimization. We engineered a class of RNA genetic controllers to modulate gene expression in yeast and mammalian cells. These RNA biosensors and switches detect small molecules, including antibiotics, antivirals, plant growth hormones, secondary metabolites, and natural products.
     To accelerate the design-build-test-learn cycle and engineer high-performance switches, we developed massively parallel assays and artificial evolution to screen tens to hundreds of thousands of sequence variants. Additionally, we applied machine learning to analyze these large, quantitative datasets, denoise results, and uncover sequence-function relationships, guiding the design of improved controllers.
     While genome-targeting approaches such as CRISPR/Cas have been widely effective, RNA targeting has emerged as a potentially safer alternative, minimizing genomic DNA disruptions. We report on the development of RNA-binding zinc finger proteins for targeted RNA modulation and RNA editing technologies for correcting disease-causing mutations. Additionally, we investigate the RNA-activating properties of SARS-CoV-2 proteins for potential treatment of loss-of-function diseases. Our findings advance the development of robust RNA-based platforms for precise gene regulation and therapeutic intervention.

BIO

Dr. Joy Xiang is an assistant professor in the Division of Biomedical Sciences at the UCR School of Medicine. She earned her B.Sc.Eng. in Biomedical Engineering from Duke University before completing her M.S. and Ph.D. in Bioengineering at Stanford University. Under Dr. Christina Smolke’s mentorship, her Ph.D. research focused on developing high-throughput approaches to engineer RNA biosensors and switches. For her postdoctoral training, she joined Dr. Gene Yeo’s lab at UCSD, where she investigated RNA-binding zinc finger proteins as RNA-targeting modules and examined the post-transcriptional regulatory networks of SARS-CoV-2 proteins. Her independent lab at UCR now aims to uncover hidden regulatory properties of RNA viruses and harness their untapped potential for developing RNA circuit elements and RNA-based therapeutics.